Nitin Karandikar, MD, PhD’s research laboratory focuses on the immune processes that underlie the pathogenesis of multiple sclerosis, which is an immune-mediated demyelinating disease of the central nervous system (CNS). His research group was the first to show the unexpected finding that CD8+ T cells targeted toward CNS antigens can suppress disease activity and could potentially be used as a therapeutic approach.
This recent study digs into the mechanism in which these CD8+ T cells help in mitigating disease. Using a mouse model of multiple sclerosis called EAE (experimental autoimmune encephalomyelitis), they show that myelin-specific CD8 T cells influence dendritic cells (DC), an important antigen presenting cell in our immune systems. CD8 T cells induced regulatory changes in both subsets of conventional DC (cDC1 and cDC2), where both adopted a mature and regulatory phenotype with an anti-inflammatory cytokine profile and a reduced capacity to support CD4+ T cell proliferation. CD8 directly interacted with cDC1 and indirectly influenced cDC2 through paracrine signaling. Single-cell RNA sequencing revealed upregulation of key immunoregulatory genes in both cDC subsets with enrichment of pathways involved in immune regulation and T cell differentiation.
This study highlights a novel mechanism in which myelin-reactive CD8+ T cells directly interact with cDC1 and modulate cDC2 through paracrine mechanisms to induce mature, regulatory dendritic cells, which leads to inhibited CD4+ T cell responses and reduced EAE pathogenesis.